Bioequivalence

Question 1

What is a generic product?

Answer 1

copy of brand name with same active ingredient for same therapuetic use

Question 2

Before bioequivalency what was the main issue causing differing performance of generics?

Answer 2

impaired absorption and F

Question 3

What was the first study to look at Cp?

Answer 3

chemicals in beaker to test blood alcohol level

Question 4

What event caused the creation of the FDC act?

Answer 4

sulfanilamide in drugs which is toxic- now this act ensures drug safety

Question 5

When was the ammendement to the FDC act that made sure drugs were efficacious not just safe?

Answer 5

1962

Question 6

What happened after the ammendment to the FDC act?

Answer 6

generic companies stopped making generics

Question 7

What act restored generic production? What does it do?

Answer 7

Drug Price competition and patent term restoration act
Made ANDA- just had to show BE

Question 8

Why did it take so long to have BE standard?

Answer 8

hard to measure [] until 1984

Question 9

Can generic companies be sued over failing to warn of a side effect NOT listed on the brand name?

Answer 9

NO

Question 10

What does pharmaceutical equivalents mean?

Answer 10

exact same amount of medical ingredients - not same non medicinal components

Question 11

What is US definition of bioavailability?

Answer 11

rate and extend of active ingredient is absorbed and reaches site of action

Question 12

What is CND definition of biovailability?

Answer 12

rate and extent of absorption of drug

Question 13

What is US definition of BE?

Answer 13

no significant difference b/w rate and extent become available at site of action

Question 14

What is CND definition of BE?

Answer 14

lots of similarity of bioavailabilities of 2 products with same dose, unlikely to produce clinically relevant differences

Question 15

What is the main difference b/w US and CND definitions of BE?

Answer 15

CND- looks at effect
US- looks at [] at site

Question 16

What are some physiological factors that affect BA?

Answer 16

membrane permeability, pH, motility, age

Question 17

What is absolute BA and relative?

Answer 17

Absolute= oral to IV
Relative= different forms by same route

Question 18

What does AUC tell you?

Answer 18

extent

Question 19

WHat tells you the rate of absorb and which is the easiest to measure?

Answer 19

ka, Tmax, Cmax
Cmax is easiest

Question 20

What is meant by apparent rate constant?

Answer 20

Ka from the drug product so dissolition and liberation also occur

Question 21

When can you waive BE test?

Answer 21

no issue with absorb, IV, topical, inhalation

Question 22

What test do we do if a PK-BE is not possible?

Answer 22

PD-BE

Question 23

What happens if you cant do a PD or PK study?

Answer 23

clinical study- usually for topicals

Question 24

When do you look at early exposure for drugs?

Answer 24

if fast acting

Question 25

What is a SOD study design?

Answer 25

2 products that wil crossover to test

Question 26

Pros of crossover

Answer 26

lowers intersubject variability, can easily replicate,lowers study size

Question 27

When do you consider doing a parallel study?

Answer 27

if drug has a very long half life or depot formulations

Question 28

What is the minimum number of subjects?

Answer 28

12

Question 29

How many samples should be collected per subject per dose? How many 1/2 lives should you measure?

Answer 29

12 sample 3 half lives

Question 30

What is a significant washout time?

Answer 30

10 half lives

Question 31

What are pros of multiple dose administration studies?

Answer 31

good for patients unethical to d/c treat get all data points

Question 32

For multiple dose studies, what parameters characterize rate and extent of BA?

Answer 32

AUC % fluctuation

Question 33

For BE in old days what was the criteria?

Answer 33

mean AUC within 20%

Question 34

What must be done to the data to statistically analyze them?

Answer 34

log trasnformed

Question 35

What is current BE criteria?

Answer 35

when log trasnformed 90% CI between 80-125%

Question 36

What are the 3 BE comparisons?

Answer 36

population individual population and individual

Question 37

What does a statistical analysis assumes?

Answer 37

Normal independent- random variables are independent homoscedasticity-variance of dependent is constant

Question 38

What test do you do if looking at variability in one patient or even between subjects?

Answer 38

ANOVA

Question 39

What is residual variance?

Answer 39

error of ANOVA estimation of within subject variance product variability

Question 40

What is a null hypothesis?

Answer 40

no difference

Question 41

DO A PRACTICE CI QUESTION

Answer 41

90%CI=100 x e^(Difference +- t(n1+n2-2) x SE difference) difference= difference in log means of T and R t= tvalue NOT time n thing= degree of freedom SE= standard error difference

Question 42

What do modified release products need? Why?

Answer 42

BE in fasted and fed WHy- more variation and s/e

Question 43

For modified release, is CI needed?

Answer 43

NO but still need to be in 80-125%

Question 44

For multiple dose MR drugs do you need to fast, fed or both?

Answer 44

fast unless need food

Question 45

For fed state what is the choice of food?

Answer 45

high calorie and high fat= more effect on git physiology

Question 46

If a drug is toxic which is better crossover or parallel?

Answer 46

parallel

Question 47

For non linear drugs if it saturates which dose should you use?

Answer 47

lowest

Question 48

For non linear drugs if it has great than expected AUC which dose should you use?

Answer 48

highest

Question 49

What is a long half life?

Answer 49

>24hrs

Question 50

What is the BE criteria for drugs with long half lives?

Answer 50

do for 3 half lives, parallel, in volunteers

Question 51

What is a critical dose drug?

Answer 51

small difference in dose lead to bad therapeutic outcomes

Question 52

What are BE requirements for CDDs?

Answer 52

90-112% both fasted and fed

Question 53

Whenis steady state studies for CDD needed?

Answer 53

in patients that already need the drug,

Question 54

What parameters are needed for combination products?

Answer 54

PK parameters assessed for each active ingredient

Question 55

What value indicates hughly variable drug?

Answer 55

>30% ANOVA-CV

Question 56

What is formula for ANOVA-CV?

Answer 56

= sqroot (residual variance) x 100%

Question 57

FOr drugs with measurable endogenous levels what should dose be?

Answer 57

high enough to differential exogenous and endogenous

Question 58

What is aqueous solubility a trait of?

Answer 58

medicinal ingredient

Question 59

What are the 4 BCS categories?

Answer 59

1= High sol, high perm 2- low sol, high perm 3- high sol, low perm 4- low, low

Question 60

What drug can only be BCS biowaivered?

Answer 60

IR

Question 61

How do you classify solubility?

Answer 61

highest dose of IR

Question 62

WHen is it high permeability?

Answer 62

>85%

Question 63

What is a Caco-2 assay?

Answer 63

for permeability

Question 64

What are the key factors for absorption?

Answer 64

solubility and permeability

Question 65

For each BCS category what is extent of absorb?

Answer 65

1- good 2- dissolution limited 3- permeability limited 4-bad

Question 66

What is max amount of excipient from reference allowed if disrupt absorption to get biowaver?

Answer 66

10%

Question 67

What is rate limiting step for category 1?

Answer 67

dissolution or gastric empty

Question 68

What is considered rapid dissolution?

Answer 68

>85% in <15 minutes

Question 69

Can you get a biowaiver if the two products are different salts?

Answer 69

only if class 1

Question 70

WHat also cant get biowaivers?

Answer 70

Class 4, narrow TI, absoprtion in oral cavity

Question 71

How to do a comparative dissolution test?

Answer 71

900 ml of medium, temp 37.1 degrees celsius, paddle to stir, 3 buffers

Question 72

What is the f2 variable?

Answer 72

similarity factor to compare for biowaiver

Question 73

What f2 value indicates similar?

Answer 73

50%

Question 74

When is a f2 test not necessary?

Answer 74

if 85% dissolved in under 15 minutes